Paired-box genes are frequently expressed in cancer and often required for cancer cell survival
Paired-box genes are frequently expressed in cancer and often required for cancer cell survival
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DOI：
10.1038/sj.onc.1206766
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发表时间：
2003-09-11
期刊：
影响因子：
8
通讯作者：
Eccles, MR
中科院分区：
文献类型：
--
作者：
Muratovska, A;Zhou, CM;Eccles, MR
配对盒(PAX)基因编码一个由9个特征良好的配对盒转录因子组成的家族，在发育和疾病中发挥重要作用。虽然PAX基因主要在胚胎中表达，但结构性表达会促进组织增殖。PAX基因罕见的肿瘤特异性突变与致癌作用有关，持续的PAX表达是几种肿瘤的特征。然而，还没有对PAX基因的表达进行全癌范围的分析，以调查PAX基因的一般作用。我们分析了PAX基因在一组常见癌细胞系中的表达模式和需求。在肿瘤细胞系中发现了非常频繁的PAX基因表达，包括淋巴瘤、乳腺癌、卵巢癌、肺癌和结肠癌。此外，PAX2基因在一组406例常见的原发肿瘤组织中频繁表达。尽管伴随着TP53和/或HRAS突变，但在RNA干扰沉默PAX2表达后，卵巢和膀胱癌细胞系迅速诱导凋亡。这些数据表明，PAX基因在癌症中频繁表达，内源性PAX基因的表达是癌细胞生长和存活所必需的。
The paired-box (PAX) genes encode a family of nine well-characterized paired-box transcription factors, with important roles in development and disease. Although PAX genes are primarily expressed in the embryo, constitutive expression promotes tissue hyperplasia. Rare tumor-specific mutations of PAX genes implicate an oncogenic role, and persistent PAX expression characterizes several tumors. Yet, a cancer-wide analysis of PAX gene expression to investigate a general role for PAX genes has not been performed. We analysed the pattern and requirement for PAX gene expression in a panel of common cancer cell lines. Very frequent PAX gene expression was identified in tumor cell lines, including lymphoma, breast, ovarian, lung, and colon cancer. In addition, the PAX2 gene was frequently expressed in a panel of 406 common primary tumor tissues. Apoptosis was rapidly induced in ovarian and bladder cancer cell lines following RNA interference to silence PAX2 expression, despite concomitant TP53 and/or HRAS mutations. These data suggest that PAX genes are frequently expressed in cancer, and that endogenous PAX gene expression is required for the growth and survival of cancer cells.